Limitations

ACTH secretion is pulsatile so multiple specimen collections may be required. Collection in nonsiliconized tubes can result in falsely low results as ACTH adheres to glass.

As with all tests containing monoclonal mouse antibodies, erroneous findings may be obtained from samples taken from patients who have been treated with monoclonal mouse antibodies or who have received them for diagnostic purposes.3 In rare cases, interference due to extremely high titers of antibodies to streptavidin and ruthenium can occur.3 The test contains additives, which minimize these effects.

Methodology

Electrochemiluminescence immunoassay (ECLIA)

Reference Interval

7.2−63.3 pg/mL (Note: For samples collected between 7 AM and 10 AM)

Additional Information

Adrenocorticotropic hormone (ACTH), or corticotropin, is a peptide hormone consisting of 39 amino acids. It is produced in the anterior pituitary of the brain as part of the precursor molecule pro-opiomelanocortin (POMC). Tissue-specific cleavage results in ACTH and a range of related peptides.1,4

ACTH stimulates formation and secretion of glucocorticoids (especially cortisol) by the adrenal cortex. The glucocorticoid production is regulated by various factors.5-8 After stimulation (eg, by physical effort or by the internal body clock), the hypothalamus secretes CRH (corticotropin-releasing hormone). CRH acts on the pituitary, which in turn synthesizes and secretes ACTH. Finally, ACTH stimulates secretion of the glucocorticoids by the adrenals. High concentrations of glucocorticoids in the blood inhibit secretion of CRH and ACTH via a negative feedback mechanism.

ACTH concentrations show a diurnal variation with high levels in the morning and low levels in the evening; therefore, as with cortisol, it is important to know the collection time of the plasma sample for interpretation of the results.

Plasma ACTH measurements are useful in the differential diagnosis of pituitary Cushing's disease (ACTH hypersecretion), autonomous ACTH-producing pituitary tumors (eg, Nelson's syndrome), hypopituitarism with ACTH deficiency, and ectopic ACTH syndrome.9,10 In addition to cortisol measurements, ACTH determinations can be used together with functional or stimulation tests to diagnose the origin of glucocorticoid overproduction. Similarly, ACTH measurements can be employed to facilitate differential diagnosis of adrenocortical insufficiency (Addison's disease).

ACTH not produced by the pituitary gland is known as ectopic ACTH;11 this is often associated with small cell carcinoma of the lung. In rare cases, ectopic ACTH can be caused by thymic tumors, pancreatic adenocarcinomas, or bronchial carcinoids. These tumors often secrete ACTH precursors (POMC and pro-ACTH).

Causes for Rejection

Clinical Information

Special Instructions

Instructions for suppression/stimulation tests involving ACTH measurement can be found in the online endocrine appendices ACTH Stimulation and Corticotropin-releasing Hormone Stimulation.

This test may exhibit interference when sample is collected from a person who is consuming a supplement with a high dose of biotin (also termed as vitamin B7 or B8, vitamin H, or coenzyme R). It is recommended to ask all patients who may be indicated for this test about biotin supplementation. Patients should be cautioned to stop biotin consumption at least 72 hours prior to the collection of a sample.